Aromatic methyl ketones in the synthesis of biologically active heterocyclic compounds

Programme

Postdoctoral program

Strategic priority

Sustainable agriculture, food security and food security

Code
21.00208.5107.05/PD
Duration
2021-2023
Institutions

Institute of Chemistry

Laboratories/Centers
Project manager

Dr., assoc. prof. POGREBNOI Serghei

Abstract

Every year, the vineyards, gardens and orchards of the Republic of Moldova are affected by Noble Rot (Botrytis cinerea), Downy mildew (Plasmopara viticola Berl. Et Toni), Oidium tuckeri (Uncinula necator), Fire blight (E. Carotovora) and other diseases, which affects a wide range of agricultural plant species. These are some of the most devastating and serious diseases, which attack the bunches and berries of grapes, the stems and leaves of potatoes, tomatoes and peppers, fruits of apples and pears, diseases that cause the vineyards and orchards damage in our country. Modern treatments have a weak effect. Farmers invest a lot in treatments, which only manage to stop the evolution of the fungus, but do not lead to the complete eradication of the disease. The high resistance of most phytopathogenic bacteria, and as a result, the total destruction of the crop is one of the most pressing problems facing agricultural producers not only in Moldova but also in other states, where the agro-industrial complex is of particular importance in the country's economy. The discovery of new effective chemical agents with a disease-healing profile, superior to existing substances and minimal toxicity, as well as their correct use in treatment, is one of the main tasks of scientists around the world. Taking into account these aspects, the present project proposes the development of hybrid molecules in an enantiomerically pure state with antimycobacterial properties.
The synthesis of the targeted compounds will focus on obtaining molecules with diterpene fragment as a source of chirality, combined with the heterocyclic fragment. The development of new hybrid materials presents a fascinating field of research, which encourages the search for new materials with high biological efficiency, thanks to the concomitant presence of heterocyclic and natural fragments. In particular, it is of interest to obtain hybrid molecules for the selective delivery of the remedy to the site of action, to improve bioavailability, to reduce the toxicity of preparations and last but not least, to minimize the resistance of phytopathogenic bacteria. All new compounds will be isolated, purified and characterized by various physico-chemical methods. The investigation of biological properties will be done using different species of pathogenic bacteria. After obtaining the results of the evaluation of the biological activity, the recommendations for their use in practice will be stipulated.

Results, activities

2021

In the course of optimizing the method, the process of isolating Dehydroabietic acid improved, and, as a result, the yield of the target product increased, and methyl ester was initially obtained on its basis. Its further acylation led to the corresponding derivative, after which bromination was carried out, followed by the reaction of the bromo derivative with 1,2,4-triazole or imidazole. As a result, new hybrid molecules with fragments of dehydroabietic acid and a heterocyclic residue, triazole or imidazole, respectively, were obtained.
It should be noted that the successful transformation of the carbonyl group into an acetylene derivative took place, and in the near future, it is planned to obtain molecules with a 1,2,3-triazole fragment by its interaction with azides.
The method is applicable for the synthesis of enantiomerically pure hybrid molecules containing a chiral diterpene base (Dehydroabietic acid residue) in combination with a heterocyclic fragment (various triazoles or imidazoles).
New compounds have been isolated, purified, and characterized by all available physicochemical methods. The study of biological properties will be carried out on various strains of pathogenic bacteria, and the results of the assessment of their biological activity will establish recommendations for practical application.
During a business trip to the State University of St. Petersburg, plans for further biological testing of the obtained compounds were discussed.

Publications

Article 

1. ZVEAGHINTSEVA, M., STINGACI, E., POGREBNOI, S., SMETANSCAIA, A., VALICA, V., UNCU, L., KRAVTSOV, V., MELNIC, E., PETROU, A., GLAMOČLIJA, J., SOKOVIĆ, M., CARAZO, A., MLADĚNKA, P., POROIKOV, V., GERONIKAKI, A., MACAEV, F.Z. Chromenols derivatives as novel antifungal agents. Synthesis, In Silico and In Vitro Evaluation biological evaluation and molecular docking. În: Molecules, 2021, 26(14), 4304. (IF: 4.411). ISSN 1420-3049 (Online) DOI: 10.3390/molecules26144304 

Patents

  1. MACAEV, F., STÂNGACI, E., POGREBNOI, S., BOLDESCU, V. Metodă pentru sinteza 3,3-dialilindolin-2-onei. Patent MD 4739B1 from 2021.01.31.  http://www.db.agepi.md/Inventions/details/a%202019%200067
    https://worldwide.espacenet.com/publicationDetails/biblio?II=1&ND=3&adjacent=true&locale=en_EP&FT=D&date=20210131&CC=MD&NR=4739B1&KC=B1

  2. MACAEV, F., ZVEAGHINȚEVA, M., STÂNGACI, E., POGREBNOI, S., LUPAŞCU, L. Utilizare a (Z)-4,4-dimetil-1-(4-nitrofenil)-2-(1H-1,2,4-triazol-1-il)pent-1-en-3-onei în  calitate de ingredient activ contra bacteriilor fitopatogene. Patent MD 4740B1 from 2021.02.28, BOPI nr.2/202 1 http://www.db.agepi.md/Inventions/details/a%202020%200056 https://worldwide.espacenet.com/publicationDetails/biblio?II=0&ND=3&adjacent=true&locale=en_EP&FT=D&date=20210228&CC=MD&NR=4740B1&KC=B1